The
design of bioactive supramolecular chirality is always hampered
by the lack of feasible schemes to assigned specific biological activities.
Herein, we developed a “mirror-image peptide grafting”
method to graft the epitopes of bioactive d-peptide onto
the miniprotein template to construct a self-assembled supraparticle.
Grafting DPMIβ, a 12-mer d-enantiomeric
peptide functioned as the p53 agonist, onto Apamin, we successfully
constructed a self-assembled d-enantiomeric miniprotein supermolecule
nanoparticle, termed DMSN. This chiral supraparticle possesses
a favorable pharmaceutical profile including the passive tumor targeting,
cell membrane penetration, intracellular reductive responsiveness,
and endosome escaping. DMSN showed in vitro and in vivo p53-dependent antiproliferative activity
and augmented antitumor immunity elicited by anti-PD1 therapy. This
enabling strategy will allow us to fabricate a class of peptide/protein-derived
supramolecular chirality with predictable biological activities and
will likely have a broad impact on the chiral nanotechnology at the
service of prevention and treatment of human diseases.
Tumor-targeted delivery of photothermal agent and controlled release of concomitant chemotherapeutic drug are two key factors for combined photothermal chemotherapy. Herein, we developed a pH/near-infrared (NIR) dual-triggered drug release nanoplatform based on hyaluronic acid (HA)-functionalized gold nanorods (GNRs) for actively targeted synergetic photothermal chemotherapy of breast cancer. Targeting folate (FA), dopamine, and adipic acid dihydrazide triconjugated HA was first synthesized and used to decorate GNRs via Au-catechol bonds, and then an anticarcinogen doxorubicin (DOX) was conjugated onto HA moieties via an acid-labile hydrazone linkage, resulting in multifunctional nanoparticles GNRs-HA-FA-DOX. The nanoparticles exhibited excellent stability and had a pH and NIR dual-responsive drug release behavior. In vitro studies showed that the nanoparticles could be efficiently internalized into breast cancer MCF-7 cells and kill them under NIR irradiation in a synergistic fashion via inducing cell apoptosis. Pharmacokinetics and biodistribution studies in tumor-bearing mice indicated that the nanoparticles had a long blood circulation with a half-life of 2.4 h and exhibited a high accumulation of 11.3% in tumor site. The tumors of mice treated with combined chemotherapy and photothermal therapy were completely suppressed without obvious systemic toxicity after 20 d of treatment. These results demonstrated a great potential of GNRs-HA-FA-DOX nanoparticles for targeted synergistic therapy of breast cancer.
A rationally designed graphene-hollow polypyrrole (PPy) nanoarchitecture in which hollow PPy spheres were inserted between graphene layers was constructed by mixing graphene oxide and polystyrene (PS)@PPy core-shell sphere, followed by reduction of graphene oxide and etching of PS. The as-prepared graphene-hollow PPy nanoarchitecture was explored as electrode material for supercapacitor applications. The specific capacitance may gradually rise to as high as 500 F g(-1) with a charging/discharging current density of 5 A g(-1), and remains stable even after 10,000 cycles. Analysis indicates that the tailored nanoarchitecture enhances specific area of the electrode and promotes synergetic effect between RGO and PPy, thus leading to a significantly enhanced electrochemical performance.
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